Positron emission tomography (PET) is a powerful tool that utilizes radioisotope-labeled molecules (PET tracers) to study the biochemistry and distribution of these molecules in the human brain. A considerable fraction of PET studies involve the use of 11C-labeled PET tracers. Due to the short half-life of the 11C-isotope (20 minutes), the synthesis of 11C-PET tracers must be preformed in an extremely short timeframe if the tracer is to retain sufficient radio-emitting properties to be useful as an imaging agent. Thus the growth of the 11C-PET technique has been closely tied to the development of new rapid synthesis and purification methods. In this proposal, we outline the development of a novel solid-phase technique that should significantly expedite the synthesis of 11C-PET tracers that should find application in a wide variety of therapeutic areas (including brain imaging). In our proposed approach, a PET tracer precursor is covalently attached to a designed polymer resin followed by the addition of cyclotron-derived hydrogen cyanide. This reaction sequence should result in the formation of the desired 11C-PET tracer as the only product. Thus, this resin-based strategy has been designed to avoid the traditional reaction purification step, leaving more time for the synthesis of PET tracers with potentially higher specific radioactivities and greater molecular complexity than previously possible. Based on various hypotheses on the mechanism of the cyanide addition reaction, a series of resins have been designed to maximize the rate of 11C-PET-tracer production. We also propose to employ this new methodology in the first 11C-synthesis of two gamma-butyric acid (GABA) receptor agonists 11C-GABOB and 11C-baclofen. CABOB has been prescribed for the treatment of epilepsy and baclofen is widely-used for the management of spasticity exhibited in multiple sclorosis, Tourette Syndrome, and dystonia. The creation of radioisotope-labeled analogs of CABOB and baclofen for PET studies should significantly further our understanding of these drugs and potentially lead to the development of new therapies for treating central nervous system diseases.